A closer look at the synthesis of 2-[18F]fluoroethyl tosylate to minimize the formation of volatile side-products

Martha Sahylí Ortega Pijeira, Sofia Nascimento dos Santos, Yasniel Babi Araujo, André Luis Lapolli, Marcio Nardelli Wandermuren, Zalua Rodríguez Riera, Ivone Carvalho, Philip H. Elsinga, Emerson Soares Bernardes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: 2-[18F]Fluoroethyltosylate ([18F]FEtOTs) is a well-known 18F-fluoroalkylating agent widely used to synthesize radiotracers for positron emission tomography. The widespread use of [18F]FEtOTs is due in part to its low volatility when compared to other halide and sulfonate building blocks. In this work, the radioactive volatile side-products formed during the synthesis of [18F]FEtOTs were identified and characterized for the first time, and an optimization of the reaction conditions to minimize their formation was proposed.

Results: In order to characterize the volatiles produced during [18F]FEtOTs synthesis, the reaction mixtures of both cold FEtOTs and [18F]FEtOTs were co-injected onto the HPLC system. The radioactive peaks corresponding to the volatile compounds were collected, analyzed through headspace gas chromatography mass spectrometry sampler (HS-GC–MS) and identified as vinyl fluoride ([19F]VF) and 2-fluoroethanol ([19F]FEOH). By using a rotatable central composite design with a two-level full factorial core of two factors (22), it was determined that temperature and time are independent variables which affect the generation of [18F]VF and [18F]FEOH during the radiosynthesis of [18F]FEtOTs. In addition, in order to reduce the formation of the volatiles ([18F]VF and [18F]FEOH) and increase the yield of [18F]FEtOTs, it was demonstrated that the molar ratio of base to precursor must also be considered.

Conclusion: [18F]VF and [18F]FEOH are volatile side-products formed during the radiosynthesis of [18F]FEtOTs, whose yields depend on the reaction time, temperature, and the molar ratio of base to precursor. Therefore, special care should be taken during the radiosynthesis and subsequent reactions using [18F]FEOTs in order to avoid environmental contamination and to improve the yield of the desired products.

Original languageEnglish
Article number26
Number of pages15
JournalEJNMMI Radiopharmacy and Chemistry
Volume7
DOIs
Publication statusPublished - Dec-2022

Keywords

  • 2-[F]fluoroethanol
  • 2-[F]Fluoroethyl tosylate
  • PET tracers
  • Radiation safety
  • Radioactive gas
  • [F]vinyl fluoride

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